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Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet]. Chichester, UK: John Wiley & Sons, Ltd; 2003-.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet].

Enzyme replacement therapy for Anderson‐Fabry disease

This version published: 2013; Review content assessed as up-to-date: December 12, 2012.

Plain language summary

Anderson‐Fabry disease is a rare X‐linked recessive (inherited) lysosomal storage disease. Lysosomal disorders are triggered when a particular enzyme exists in too small an amount or is missing altogether; thus substances that should be broken down by the enzyme and recycled build up in the cell. This can cause a wide range of symptoms which affect the entire body. The kidneys, heart and brain can be affected and this can result in major illness and reduced life expectancy among affected individuals. Symptomatic males and females with Anderson‐Fabry disease have been described within the literature, although the appearance of clinical signs may be delayed and more variable among females.

The review is based on six clinical trials that enrolled 223 participants. The trials used different formulations of the enzyme. Two trials compared agalsidase alfa to placebo; three trials compared agalsidase beta to placebo; and one trial compared agalsidase alfa to agalsidase beta. We analysed the three sets of data separately. Limited evidence from six small poor quality randomised controlled trials shows no robust evidence for use of both agalsidase beta and alfa to treat Anderson‐Fabry disease. New trials should be undertaken with adequate sample size to detect possible differences among the treatment groups. Evaluating the same clinical outcomes should clarify the comparable effects of using the two current enzyme formulations (i.e. agalsidase alfa and agalsidase beta). Data on outcomes are being prospectively collected through surveillance or registry‐based programs, as post‐marketing commitments made by the sponsors.

Abstract

Background: Anderson‐Fabry disease is an X‐linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio‐ and cerebro‐vascular involvement. Survival is reduced among affected males and symptomatic female carriers.

Objectives: To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson‐Fabry disease.

Search methods: We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.

Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012.

Selection criteria: Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson‐Fabry disease.

Data collection and analysis: Two authors selected relevant trials, assessed methodological quality and extracted data.

Main results: Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.

Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non‐significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference ‐2.10 (95% confidence interval (CI) ‐3.79 to ‐0.41); at up to five months, mean difference ‐1.90 (95% CI ‐3.65 to ‐0.15); and at up to six months, mean difference ‐2.00 (95% CI ‐3.66 to ‐0.34). There was a significant difference in pain‐related quality of life at over five months and up to six months, mean difference ‐2.10 (95% CI ‐3.92 to ‐0.28) but not at other time‐points. Neither trial reported deaths.

One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference ‐1.70 (95% CI ‐2.09 to ‐1.31); heart, mean difference ‐0.90 (95% CI ‐1.18 to ‐0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference ‐4.80 (95% CI ‐5.45 to ‐4.15). There was no significant difference between groups for death; no trials reported on pain.

Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57).

Authors' conclusions: Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson‐Fabry disease.

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group.

Publication status: New search for studies and content updated (no change to conclusions).

Citation: El Dib RP, Nascimento P, Pastores GM. Enzyme replacement therapy for Anderson‐Fabry disease. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD006663. DOI: 10.1002/14651858.CD006663.pub3. Link to Cochrane Library. [PubMed: 23450571]

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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